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The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis. | LitMetric
Purpose : Mutations in TCP-1 ring complex (TRiC) have been associated with Leber Congenital Amaurosis (LCA). TRiC is involved in protein folding and has 8 essential subunits including CCT5. Herein, we studied the retina of TRiC mutant zebrafish to evaluate the possible role of impaired actin and tubulin folding in LCA.Methods : The retina was histologically studied using Toluidine Blue staining as well as TUNEL, BrdU-labeling, and Phalloidin assays. Retinal organisation was assessed by quantification of the cellularity utilising DAPI.Results : Laminar organization of retinas was intact. Enhanced apoptosis throughout the retina was not compensated by higher proliferation rates, leaving the retina smaller in size. Quantification of retinal layer cellularity demonstrated that specifically the numbers of the amacrine and the retinal ganglion cells were depleted, suggesting that the retina was not uniformly affected by the reduced actin folding.Conclusion : Whereas the current literature suggests that LCA is predominantly affecting retinal photoreceptor cells and the retinal pigment epithelium, analyses demonstrated the important role of folding of actin by TRiC, suggesting that is a useful tool to specifically analyze the role of F-actin filaments in the context of LCA.
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